An activated, or functionalized, layer that is bonded or otherwise disposed on the surface of a substrate is useful as an interface between the substrate and other materials such as organic or metallic materials. This functionalized layer allows the substrate to react with and to bind to the organic or metallic material.
The need for control of infection is a vital concern for many, from public health officials, hospital and school administrators and the like, to private citizens. Typically, control of infection can be achieved by the topical application of disinfectants, antiseptics, antibacterials and the like to surfaces likely to be contacted by infectious agents. Common disinfectants include active chlorine such as hypochlorites, chloramines, dichloroisocyanurate and trichloroisocyanurate, wet chlorine, chlorine dioxide and the like, active oxygen, including peroxides, such as peracetic acid, potassium persulfate, sodium perborate, sodium percarbonate and urea perhydrate, iodine compounds such as iodpovidone, iodine tincture, iodinated nonionic surfactants, concentrated alcohols such as ethanol, n-propanol and isopropanol and mixtures thereof; 2-phenoxyethanol and 1- and 2-phenoxypropanols, phenolic compounds, cresols, halogenated phenols, such as hexachlorophene, triclosan, trichlorophenol, tribromophenol, pentachlorophenol, Dibromol and salts thereof, cationic surfactants, including quaternary ammonium cations such as benzalkonium chloride, cetyl trimethylammonium bromide or chloride, didecyldimethylammonium chloride, cetylpyridinium chloride, benzethonium chloride and others, and non-quaternary compounds, such as chlorhexidine, glucoprotamine, octenidine dihydrochloride etc.); strong oxidizers, such as ozone and permanganate solutions; heavy metals and their salts, such as colloidal silver, silver nitrate, mercury chloride, phenylmercury salts, copper, copper sulfate, copper oxide-chloride and the like, and strong acids (phosphoric, nitric, sulfuric, amidosulfuric, toluenesulfonic acids) and alkalis (sodium, potassium, calcium hydroxides). However, many of these compounds are harmful to mammalian tissue. Moreover, these compounds only have a short-term effect, and need to be reapplied constantly.
Antibiotics can be administered to stop infection in individuals. However, such administration is not always effective. Numerous medical applications, including orthopaedic, trauma, spine and general surgery applications, where the potential for infection is a serious concern, are not amenable to simple application of antiseptic or treatment with antibiotics. For example, infection can be a devastating complication of a total joint arthroplasty (TJA). While some infections may be treated by antibiotic suppression alone, more aggressive therapies, such as two-stage re-implantation, are often required. The treatment of post-arthroplasty infections in 1999 cost over $200 million in the US alone. Spangehl, M. J., et al., J. Bone Joint Surg. Am., 1999, 81(5), 672-682. TJA infections occur when bacteria colonize the surface of the implant. These species then form a resistant biofilm on the implant surface, which nullifies the body's normal antibody response.
External fixation devices provide temporary but necessary rigid constraints to facilitate bone healing. However, patients risk pin-tract infection at the site extending from the skin-pin interface to within the bone tissue. Such complications can result in sepsis and osteomyelitis, which could require sequestrectomy for correction. Even the most stringent pin-handling and post-procedure protocols have only a limited effect. Studies have shown that such protocols do not reduce the chance of infection. Davies, R., et al. J. Bone Joint Surg. Br., 2005, 87-B, 716-719.
In minimally-invasive spine fusions, pedicle screws are first implanted in the bone of the vertebrae, and then rods are fixed into the heads of the screws to immobilize and stabilize the affected segments. Screws and rods pass through the patient's skin into the spine space via a cannulated channel. As in external fixation, screws and rods are also prone to pin-tract infections; due to the implants' pathway through the skin, the chance of contacting and/or passing harmful bacteria is greatly increased.
Catheters and shunts are placed in any number of body cavities and vessels to facilitate the injection, drainage, or exchange of fluids. Infections are common in catheter placements and are largely dependent on how long the patient is catheterized. For example, Kass reports an infection rate of virtually 100% for patients with indwelling urethral catheters draining into an open system for longer than 4 days. Kass, E. H., Trans. Assoc. Am. Physicians, 1956, 69, 56-63.
Therefore, there is a need for anti-infective surfaces that may be employed in locations particularly susceptible to hosting infectious agents, such as public places, common areas of buildings, fixtures and the like. Moreover, there is a need for substrates and materials with anti-infective surfaces, such as medical devices including implants, screws, rods, pins, catheters, stents, surgical tools and the like which could prevent infections by proactively killing bacteria that attempt to colonize the device surface both pre- and post-operatively.